Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with the stages of development. Prior to differentiation into liver cells, the cells express genes involved in the cell cycle, DNA replication, and proliferation. Later in development, genes involved in epithelial differentiation and blood coagulation are highly expressed. Once cells differentiate into hepatocytes, the expression of genes involved in liver-specific functions increases, such as those involved in lipid metabolism and cholesterol regulation.
Gene expression can be regulated at many points including transcription, translation, RNA processing and transport, and post-translational modifications. Common methods of regulating expression are factors that bind directly to DNA to regulate the transcription of a particular gene. Gene expression in the liver can be regulated by the transcription factors C/EBPα, C/EBPβ, and Hepatocyte Nuclear Factor-1, among others. Regulation can occur prior to transcription by altering the histones contained in chromatin. These modifications result in either loosening or tightening of the DNA structure, thereby respectively preventing or allowing transcriptional regulators to access the DNA. Different cell types have different covalent modifications and histone variants, which results in the variation in gene accessibility.
Cells are subject to environmental changes and express different genes in response to these extracellular stimuli. Glucose is an important source of energy, and as its concentration in the bloodstream fluctuates, an organism must respond with appropriate changes in gene and protein expression. When blood glucose levels decrease, the pancreas secretes the hormone glucagon. This hormone signals the liver to initiate the production of phosphoenolpyruvate carboxykinase (PEPCK), a protein required to produce glucose from non-carbohydrate precursors. Glucagon induces the transcription of this gene by indirectly stimulating transcription factors C/EBPα and C/EBPβ to bind to the PEPCK promoter. When blood glucose levels are high, the pancreas secretes the hormone insulin; the PEPCK gene has an insulin-responsive sequence that inhibits its transcription.
